Rouhani's visit to Paris is expected to result in the signing of important business contracts, after sealing multi-billion dollar deals in Italy.
A major order for 114 Airbus planes to modernise Iran Air's ageing fleet is expected to be confirmed in France, along with tie-ups with carmakers Peugeot and Renault.
Before heading to Paris, Rouhani will conclude his two-day trip to Rome with a visit to the Colosseum with Italian Culture Minister Dario Franceschini.
The president is accompanied by a delegation of more than 100 ministers, officials and businessmen marking the return of Iran on the international economic stage with the lifting of sanctions after a historic deal over Tehran's nuclear programme.
Rouhani, a 67-year-old former academic and diplomat who is seen as a pragmatist, was elected in 2013 on a pledge to end sanctions and improve relations with the West.
The Iranian leader on Monday met with his Italian counterpart Sergio Mattarella and Prime Minister Matteo Renzi, with whom he attended the signing of several economic agreements in the prestigious setting of the Capitole.
Italian officials said contracts signed in Rome would be worth up to 17 billion euros ($18.4 billion), underlining the huge economic stakes involved in Iran's re-opening, particularly for Europe's manufacturing and engineering sectors.
On Monday, Rouhani attended a business forum at which he portrayed Iran as the ideal base for companies seeking a foothold in a region of 300 million people, reassuring would-be investors their contracts would be honoured.
"Iran is the safest, the most stable country in the entire region," Rouhani said.
"Everyone understood that the nuclear negotiations represented a win-win situation for both sides.
"Now we have created the conditions for investment and for the transfer of know-how. There has to be an advantage for both sides: we invite you to invest and we will provide stability and ensure that you can make adequate returns."
Rouhani then visited the Vatican for the first time and met Pope Francis, who has urged Iran to work for peace in the Middle East.
In a statement afterwards, the Vatican said Francis had urged the Iranian leader to use Iran's important role to promote, together with other countries, "adequate political solutions" to the problems afflicting the region and to help combat terrorism and arms trafficking.
It was the first official visit to the Vatican by an Iranian president since Mohammad Khatami was hosted by John Paul II in 1999.
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'Modernising our fleet'
Rouhani is due to arrive late Wednesday afternoon in Paris where he will meet the following day with President Francois Hollande and French business leaders.
Ahead of Rouhani's European trip, Iranian Transport Minister Abbas Akhoundi on Sunday announced a major contract with Airbus for 114 planes.
Akhoundi, quoted by Iranian media, said the deal "will be signed between Iran Air and Airbus" when Rouhani is in Paris. An Airbus spokesman declined to comment.
Akhoundi's deputy, Asghar Fakhrieh Kashan, told AFP that Iran "essentially wants to buy Airbus A320s, A321s and A330s".
"We will take delivery in 2016 and 2017 of Airbus A320s and A321s, with the A330s coming later," he said.
"From 2020, we will take delivery of Airbus A350s and A380s. We want eight A380s and 16 A350s."
Before flying to Europe, Rouhani himself mentioned economic projects between Iran and France.
"We need to modernise our aviation fleet and buy locomotives," he said Monday.
He indicated Iran was also looking at the automotive sector.
"Important contracts will probably be signed on this trip including with Peugeot and Renault," he said.
A joint press conference is planned after Rouhani's meeting with Hollande on Thursday, the French presidency said.
Iran has been rebuilding its relations with Italy and France which were among Tehran's main economic partners before the tightening of international sanctions in January 2012.
Competition to tap the Iranian market has been fierce as it emerges from international isolation with the lifting of sanctions.